Hypoxic MSC-Derived Extracellular Vesicles Target Photothermal Injury Induced Oxidative Stress to Protect the Facial Nerve

ABSTRACT: Endoscopic surgery has been increasingly adopted because of its minimally invasive nature and superior visualization; however, it relies on prolonged high-intensity illumination, and the neurobiological consequences of photothermal exposure to the facial nerve remain poorly understood. Here, we established a rat model of facial nerve photothermal injury and demonstrated that photothermal exposure induced significant facial nerve dysfunction, accompanied by electrophysiological impairment and structural disruption. Mechanistic analyses demonstrated pronounced accumulation of reactive oxygen species (ROS) and lipid peroxidation in both in vivo and in vitro models, identifying oxidative stress as a central mediator of photothermal injury. Based on this, hypoxia-preconditioned mesenchymal stem cell derived small extracellular vesicles (hypo-sEVs) were employed as a targeted antioxidative intervention. Proteomic profiling revealed enrichment of antioxidant-associated molecular signatures in hypo-sEVs. Functionally, hypo-sEVs attenuated oxidative stress and promoted the survival, proliferation, and migration of Schwann cells. In the rat facial nerve injury model, local delivery of hypo-sEVs using a hydrogel system significantly improved facial nerve functional recovery, electrophysiological conduction, and histological integrity. RNA-seq further demonstrated that hypo-sEVs treatment modulated gene programs related to neural repair, extracellular matrix remodeling, and oxidative stress regulation. Together, these findings identify photothermal exposure as an underrecognized contributor to facial nerve injury during endoscopic surgery and propose a ROS-oriented therapeutic strategy to mitigate neuroinflammation and promote neural repair.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE346995 | GEO | 2026/09/13

REPOSITORIES: GEO